tailieunhanh - PSYCHIATRY, PSYCHOANALYSIS, AND THE NEW BIOLOGY OF MIND - PART 7

và các hình thức nhất định của động kinh. Những dị tật này đã được chứng minh cư trú tại một hoặc một kênh ion điện áp hay ligand-gated cơ. Những rối loạn này do đó được gọi là các channelopathies rối loạn chức năng kênh ion | Neural Science 239 been made in elucidating the defects that underlie the hereditary myotonias periodic paralysis and certain forms of epilepsy. These defects have now been shown to reside in one or another voltage- or ligand-gated ion channels of muscle. These disorders therefore are now referred to as the channelopa-thies disorders of ion channel function for review see Brown 1993 Cowan et al. 1999 Ptácek 1997 1998 . As can be inferred from our earlier discussions the remarkable progress in understanding these diseases can be attributed directly to the extensive knowledge about ion channel function that was already available. For example hyperkalemic periodic paralysis and paramyotonia congenita two channelopathies due to ion channel disorders that result from mutations in the a subunit of the Na channel are caused by a number of slightly different dominant mutations that make the Na channel hyperactive by altering the inactivation mechanisms either by changing the voltage dependency of Na activation or by slowing the coupling of activation and inaction for reviews see Brown 1993 Ptácek et al. 1997 . As was already evident from earlier physiological studies rapid and complete inactivation of the Na channel is essential for normal physiological functioning of nerve and muscle cells Catterall 2000 . These mutations do not occur randomly but in three specific regions of the channel the inactivation gate the inactivation gate receptor and the voltage sensor regions that have been shown to be functionally important by the earlier biophysical and molecular studies. In contrast to these particular monogenic diseases the identification of the genetic basis of other degenerative neurological disorders has been slower. Nevertheless in some complex diseases such as Alzheimer s disease appreciable progress has been made recently. This disease begins with a striking loss of memory and is characterized by a substantial loss of neurons in the cerebral cortex the hippocampus the

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